Effect of BRCA Mutations on Metastatic Relapse and Cause-specific Survival After Radical Treatment for Localised Prostate Cancer

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Elena Castro a,b,*, Chee Goh b, Daniel Leongamornlert b, Ed Saunders b, Malgorzata Tymrakiewicz b, Tokhir Dadaev b, Koveela Govindasami b, Michelle Guy b, Steve Ellis c, Debra Frost c, Elizabeth Bancroft b, Trevor Cole d, Marc Tischkowitz e, M. John Kennedy f, Jacqueline Eason g, Carole Brewer h, D. Gareth Evans i, Rosemarie Davidson j, Diana Eccles k, Mary E. Porteous l, Fiona Douglasm, Julian Adlard n, Alan Donaldson o, Antonis C. Antoniou c, Zsofia Kote-Jarai b, Douglas F. Easton c, David Olmos a,*,y, Rosalind Eeles, Effect of BRCA Mutations on Metastatic Relapse and Cause-specific Survival After Radical Treatment for Localised Prostate Cancer, European Urology., 2015

Abstract

Background: Germline BRCA mutations are associated with worse prostate cancer (PCa) outcomes; however, the most appropriate management for mutation carriers has not yet been investigated. Objective: To evaluate the response of BRCA carriers to conventional treatments for localised PCa by analysing metastasis-free survival (MFS) and cause-specific survival (CSS) following radical prostatectomy (RP) or external-beam radiation therapy (RT). Design, setting, and participants: Tumour features and outcomes of 1302 patients with local/locally advanced PCa (including 67 BRCA mutation carriers) were analysed. RP was undergone by 535 patients (35 BRCA); 767 received RT (32 BRCA). Median follow-up was 64 mo. Outcome measurements and statistical analysis: Median survival and 3-, 5-, and 10-yr survival rates were estimated using the Kaplan-Meier method. Generated survival curves were compared using the log-rank test. Cox regression analyses were used to assess the prognostic value of BRCA mutations. Results and limitations: A total of 67 BRCA carriers and 1235 noncarriers were included. At 3, 5, and 10 yr after treatment, 97%, 94%, and 84% of noncarriers and 90%, 72%, and 50% of carriers were free from metastasis ( p < 0.001). The 3-, 5- and 10-yr CSS rates were significantly better in the noncarrier cohort (99%, 97%, and 85%, respectively) than in ...

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Type of material: Journal Article